The most prevalent pharmaceutical dosage forms at present, the porous, oral-delivery tablets, are manufactured by mixing and compacting drug and excipient powders. Although powder processing is extensively used in the manufacture of oral dosage forms, it has inherent limitations: mixing is fraught with particle segregation and agglomeration, and compacting with non-deterministic porosity. As a result, the dosage form microstructure, drug content, and drug release rate are difficult to control tightly, and their range is limited. Moreover, dosage form manufacture is by a resource-intensive and time-consuming batch process. Further details about the design and manufacture of state-of-the-art dosage forms are given in the commonly owned references “Remington's Pharmaceutical Sciences XVIII”, A. R. Gennaro (ed.), Mack Publishing, Easton, Pa., 1990; M. E. Aulton, K. M. G. Taylor, “Aulton's pharmaceutics: The design and manufacture of medicines”, fourth edition, Churchill Livingstone, London, U K, 2013; F. J. Muzzio, T. Shinbrot, B. J. Glasser, “Powder technology in the pharmaceutical industry: the need to catch up fast”, Powder Technol. 124 (2002) 1-7; T. A. Bell, “Challenges in the scale-up of particulate processes—an industrial perspective”, Powder Technol. 150 (2005) 60-71; and “Pharmaceutical Manufacturing Handbook: Regulations and Quality”, S. Cox Gad (Ed.), John Wiley & Sons, Inc., Hoboken, N.J., 2008.
The difficulties associated with processing powders could be circumvented, however, by transitioning to the predictable liquid-based processing. Therefore, in the commonly owned U.S. patent application Ser. No. 14/907,891, the U.S. patent application Ser. No. 15/482,776, and the publications in J. Control. Release, 220 (2015) 397-405; Eur. J. Pharm. Biopharm, 103 (2016) 210-218; Int. J. Pharm. 509 (2016) 444-453; Chem. Eng. J. 320 (2017) 549-560; Mater. Sci. Eng. C 80 (2017) 715-727; and Mater. Sci. Eng. C 84 (2018) 218-229, the present inventors (Blaesi and Saka) have introduced cellular and fibrous dosage forms. These dosage forms comprise solid frameworks of a drug-excipient composite (or a solid solution) and gas-filled cells or voids. It was shown that both the microstructure and the drug release rate are predictable and precisely controllable; the release rate was predominantly determined by the physico-chemical properties of the excipient, the connectivity of the void space, the cell size (or inter-fiber spacing in the case of fibrous dosage forms), and the wall thickness (or fiber radius).
In this disclosure, a method and an apparatus for the manufacture of fibrous structures are presented. The disclosed method and apparatus enable speedily and economical manufacture of dosage forms with precisely controlled microstructure and properties. They further enable the manufacture of dosage forms with a greater range of properties (e.g., a greater range of the drug release rate, drug content, etc.), and the continuous manufacture of personalized dosage forms, among others.